Drug Interaction Potentiation Clinical Trial
Official title:
YouScript IMPACT (Improving Medication Protocols and Abating Cost of Treatment) Registry
This multicenter observational study aims to investigate the benefits of providing pharmacogenetic testing with the YouScript Personalized Prescribing System which includes a clinical decision support tool and individualized pharmacist recommendations to elderly polypharmacy patients who are most at risk of adverse drug events. The YouScript system is unique in identifying drug-gene, and drug-drug-gene interactions that are missed by existing systems, and represent over 35% of significant interaction warnings. Data analysis will assess the impact of recommendations for medication changes on clinical decision making, patient outcomes, and healthcare resource utilization to determine which medications, specialties, or patient segments derive the greatest benefit from this intervention. Data gathered from patients enrolled in this study will be compared to patients matched on key characteristics from Inovalon's MORE2 healthcare database.
BACKGROUND AND RATIONALE:
Genelex Corporation is a leader in comprehensive medication management based on the
YouScript clinical decision support tool and DNA drug sensitivity testing. Controlling
prescription drug adverse event risk is complex because more than 85% of patients have
significant DNA based variation in activity of the cytochrome p450 (CYP) enzymes that
metabolize the majority of the most commonly prescribed medicines. Polypharmacy, common in
the elderly and chronically ill further increases the risk of an adverse drug event (ADE).
The public healthcare problem resulting from these factors costs an estimated $289 billion
per year in excess health care costs.
The goal of the YouScript personalized prescribing system is to improve patient outcomes by
preventing ADEs caused by drug-drug, drug-gene and drug-drug-gene interactions. ADEs are
defined to include prescription and over-the-counter (OTC) drug overdose toxicity, adverse
drug reactions (ADRs), and treatment failures generally caused by properly prescribed
medications. The YouScript system prevents ADEs by the combined analysis of patient drug
regimens and individual genetics. YouScript DNA drug sensitivity testing includes five
enzymes in the cytochrome P450 (CYP) group (CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5).
YouScript synthesizes decades of publicly funded basic and clinical research to provide
actionable information to physicians treating patients.
Elderly patients are at greater risk of an ADE. Two-thirds of adults age 65 or older take
one or more prescription drugs daily. Patients age 60 years and older account for 10-17% of
hospitalizations and 51% of the deaths from ADEs, although this age group represents just
17% of the U.S. population. Following discharge, 50% of patients with ADRs declined in one
or more activities of daily living, compared to 24% of patients without ADRs.
Although the value of pharmacogenetic testing and comprehensive gene-based medication
management is being recognized by clinicians, it is still not endorsed by many expert
committees and third party payers for most prescription drugs. The purpose of this study is
to meet the need for evidence that better demonstrates the impact of such comprehensive
gene-based medication management on healthcare resource utilization (HRU), clinical
decision-making, and patient outcomes. Therefore, the proposed study aims to assess the
impact of the YouScript Personal Prescribing System on HRU, clinical decision-making, and
clinical outcomes.
OBJECTIVES:
Primary objective:
To determine the impact of the YouScript Personalized Prescribing System on HRU.
Secondary objectives:
To assess the impact of the YouScript Personalized Prescribing System on clinical
decision-making, including risk modification through dosage adjustment and medication
change.
To assess the impact of the YouScript Personalized Prescribing System on the number of ADEs
experienced by patients.
STUDY DESIGN:
The study is designed as a prospective, non-interventional, observational study to assess
the real-world impact of the YouScript Personalized Prescribing System on HRU, provider
clinical decision-making, and ADEs. The decision to utilize the YouScript Personalized
Prescribing System and all treatment decisions will be made in accordance with usual care
practice, and will be made prior to the decision to participate in the study.
Outcomes will be compared between a group of prospectively enrolled patients undergoing
CYP2D6, CYP2C19, CYP2C9, VKORC1, CYP3A4, and CYP3A5 testing with the YouScript Personalized
Prescribing System at the discretion of their provider (i.e. "tested" patients) and data
from a group of similar patients included in Inovalon's MORE2 healthcare database meeting
the same enrollment criteria (excluding the YouScript testing) and matched on key
characteristics to the tested patients using propensity score matching. Sites will be
queried regarding use of other drug-drug interaction (DDI) systems to better distinguish the
impact of YouScript vs. other systems.
The study aims to initially enroll 1500 patients from 3-15 sites in the United States,
identified by Genelex. The study may be expanded up to 10,000 patients at additional sites
in the United States. The study duration is estimated to be at least 15 months, including 3
months for study set-up, 6 months or longer for patient enrollment depending on the rate of
accrual at each site, 4 months of per-patient follow-up and 2 months for study closeout.
A pilot study consisting of the first 150 patients enrolled will be conducted prior to
continuing enrollment in order to assist with planning the larger-scale study, such as
confirming appropriate length of follow-up necessary to observe patient outcomes, comparison
of patient baseline characteristics, identifying potential variables for propensity score
matching, sample size calculation, and necessary changes to case report forms.
After a discussion about the study with study staff and providing informed consent, baseline
data will be collected (described in more detail below), including a buccal swab or blood
sample, from patients undergoing YouScript testing. Follow-up data will be collected 120
days after enrollment on all patients. Patients will be seen in the clinic or phoned (if a
visit is not scheduled in 120 days ± 14 days from baseline) and queried regarding HRU
(including number of hospitalizations, ER visits, provider office visits, and procedures),
changes in medications, reason for changes, and adverse drug events. This data will also be
abstracted from the medical record for completeness. In addition, providers utilizing
YouScript will also be surveyed regarding the usefulness of YouScript in their clinical
decision-making.
Similar available data will be abstracted for a sample of presumably untested patients
included in the MORE2 registry database who meet eligibility criteria and are matched to
prospectively enrolled patients on key characteristics using propensity score matching.
CLINICAL ASSESSMENTS:
As this is an observational study, there are no mandatory visits. While the timing of actual
patient visits will occur at the discretion of the treating provider, it will be requested
that data be entered at baseline and again 120 days after enrollment regardless of the
number of times that a patient had been seen during that interval. All data will be
collected and entered by the sites directly into a web-based electronic data capture (EDC)
system via electronic case report forms (eCRFs).
After patients are screened and consented, the following variables will be collected at
baseline, with some being collected as part of the standard YouScript requisition form:
demographics, current smoking status, active medical conditions, liver or kidney
dysfunction, drugs of interest and other concomitant medications (including date of
initiation of therapy, dose, frequency, and indication, respectively), previous ADEs to any
drug of interest, and buccal swab/blood sample for YouScript testing. The site will not be
required to enter data collected on the YouScript requisition form into the eCRF.
The following follow-up data will be collected during a routinely scheduled visit, or by
phone if a visit is not scheduled, approximately 120 days after enrollment: number of
hospitalizations; ER visits, diagnostic or surgical procedures, and office visits since
baseline; Change/consider/monitor recommendations for drug regimen change(s) by the pharmacy
team; changes in drug regimen/dose for drugs of interest and concomitant medications since
baseline; reason for changing or not changing drug regimen/dose; ADEs since baseline; and
healthcare provider survey/questions regarding role and usefulness of YouScript in clinical
decision making. If a visit is not scheduled at 120 days ±14 days, the study staff will
contact patients by telephone and data will be collected. If patients choose to terminate
participation before completion of the 120-day follow--‐up, all follow-up data will be
collected, as well as the reason for discontinuation.
DATA ANALYSIS:
Complete analytical specifications, including tables and listings, will be fully detailed in
the statistical analysis plan (SAP). Descriptive analyses will be performed to gain an
understanding of the qualitative and quantitative nature of the data collected and the
characteristics of the sample studied. Summary statistics will be calculated and presented
for baseline characteristics and outcomes for tested and control groups separately.
Comparative analyses will be conducted to determine whether there are statistically
significant differences in specific quantitative outcomes between tested and control groups.
Because of propensity score matching between tested and control patients, unadjusted
comparative analysis will be performed and reported as the primary results. Adjusted
analysis using multiple regression models will be used to examine potential confounding
effects that cannot be addressed by the matching process. Exploratory analyses will be
conducted to explore the impact of YouScript in various subgroups and to identify potential
subgroups which will be most likely to benefit from YouScript, as deemed appropriate.
The first interim analysis will be conducted after data collection is complete for
approximately the first 150 prospectively enrolled patients (i.e. the pilot study) to
determine if any changes are necessary in the methods of the larger scale study. The second
interim analysis will be completed after data collection is complete for approximately 750
prospectively enrolled patients.
For the main analyses, differences in HRU at the 120-day follow-up will be determined by
comparing the mean number of hospitalizations, emergency room visits, diagnostic procedures,
surgical procedures, and clinic visits between the tested and untested groups. The impact of
YouScript on clinical decision making will be determined by comparing the mean number of
changes in drug regimen or dose between those who underwent YouScript testing and those that
did not. In addition, the number of ADEs experienced by patients during the 120-day study
will be compared between the tested and untested groups. Comparisons will be made with the
t-test (if the data are normally distributed), the Wilcoxon-Rank-Sum test (if the data are
continuous and not normally distributed), or the chi-squared (or Fisher exact) test if the
data are considered categorical. Multivariable linear regression models will be used to
examine the association of the YouScript Personalized Prescribing System with HRU, clinical
decision making, and ADEs, respectively, while controlling for potential confounding effects
from baseline characteristics not included in the propensity score matching process.
In tested patients only, HRU, number of ADEs, and number of changes in drug regimen/dose
will be examined in relationship to genotype, sample size permitting. Reasons for not
changing drug regimen or dose when a recommendation was made will be summarized
qualitatively or be analyzed quantitatively if possible. In addition, calculation of the
drug-gene, drug-drug-gene and drug-drug interaction recommendation acceptance rate (as
defined by whether a drug or dose was changed after a recommendation was made) will be
calculated. Provider feedback regarding whether the YouScript Personalized Prescribing
System impacted their clinical decisions will be summarized quantitatively and
qualitatively.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03789032 -
Study to Evaluate the Effect of Rabeprazole on the Pharmacokinetics of Vadadustat
|
Phase 1 | |
Completed |
NCT03706222 -
Drug-Drug Interactions of Grazoprevir/Elbasvir in Taiwan
|
||
Completed |
NCT02485028 -
Pharmacokinetic Interaction Study of Dapoxetine 30mg and Mirodenafil 50mg
|
Phase 1 | |
Completed |
NCT01896557 -
Ranitidin Versus Omeprazole in Patients Taking Clopidogrel
|
Phase 4 | |
Completed |
NCT03011463 -
Pharmacokinetic Interaction Between Trospium With an Inhibitor of OCT1 and of P-gp in Subjects Genotyped for OCT1
|
Phase 1 | |
Completed |
NCT02485041 -
Pharmacokinetic Interaction Study of Dapoxetine 30mg and Mirodenafil 100mg
|
Phase 1 | |
Completed |
NCT01477411 -
A Drug-Drug Interaction Study of Digoxin and PA21
|
Phase 1 | |
Completed |
NCT01477424 -
A Drug-Drug Interaction Study of Warfarin and PA21
|
Phase 1 | |
Completed |
NCT05558150 -
Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Ilaprazole and Aceclofenac
|
Phase 1 | |
Completed |
NCT03493698 -
A Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects
|
Phase 1 | |
Completed |
NCT03126578 -
Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam
|
Phase 1 | |
Completed |
NCT01369186 -
Drug Drug Interactions of Aspirin and P2Y12-inhibitors
|
Phase 4 | |
Completed |
NCT02378220 -
Pharmacogenetic Testing Among Home Health Patients
|
N/A | |
Completed |
NCT01324752 -
A Drug-Drug Interaction Study of Losartan and PA21
|
Phase 1 | |
Completed |
NCT02500667 -
A Drug-Drug Interaction Study of N91115 +/- Rifampin in Healthy Adult Subjects
|
Phase 1 | |
Completed |
NCT03801733 -
Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
|
Phase 1 | |
Completed |
NCT03801746 -
Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin
|
Phase 1 | |
Completed |
NCT03801759 -
Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide
|
Phase 1 | |
Completed |
NCT01736371 -
Analysis of Cisatracurium Consumption in Balanced Anesthesia With 1% Sevoflurane, and With Only Sevoflurane, Using a Closed-loop Computer Controlled System Infusion.
|
N/A | |
Completed |
NCT05237297 -
Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Naproxen, Aceclofenac, Celecoxib and Ilaprazole
|
Phase 1 |